We found that TRPC5-regulated autophagy contributes to development of chemotherapy resistance in drug sensitive breast cancer cells and maintenance of drug resistance in MCF-7/ADM cells, which is linked to Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ)/ AMP-activated protein kinaseα (AMPKα)/ mammalian target of rapamycin (mTOR) signaling pathway. The gene discussed is CAMKK2; the disease is breast cancer.